Quantification of rhBMP2 in bioactive bone materials  

作　　者：Huan Lian Han Wang Qianqian Han Chunren Wang 

机构地区：[1]Division of Biomaterials,Department of Medical Devices,National Institutes for Food and Drug Control,No.31 Huatuo Road,Beijing 102629,China

出　　处：《Regenerative Biomaterials》2020年第1期71-75,共5页再生生物材料（英文版）

基　　金：This work was supported by the China National keypoint research and invention program of the thirteenth(Project ID:2016YFC1102304).

摘　　要：Bone morphogenetic protein(BMP),belongs to transforming growth factor-b(TGF-b)superfamily except BMP-1.Implanting BMP into muscular tissues induces ectopic bone formation at the site of implantation,which provides opportunity for the treatment of bone defects.Recombinant human BMP-2(rhBMP-2)has been used clinically,but the lack of standard methods for quantifying rhBMP-2 biological activity greatly hindered the progress of commercialization.In this article,we describe an in vitro rhBMP-2 quantification method,as well as the data analyzation pipeline through logistic regression in RStudio.Previous studies indicated that alkaline phosphatase(ALP)activity of C2C12 cells was significantly increased when exposed to rhBMP-2,and showed dose-dependent effects in a certain concentration range of rhBMP-2.Thus,we chose to quantify ALP activity as an indicator of rhBMP-2 bioactivity in vitro.A sigmoid relationship between the ALP activity and concentration of rhBMP-2 was discovered.However,there are tons of regression models for such a non-linear relationship.It has always been a major concern for researchers to choose a proper model that not only fit data accurately,but also have parameters representing practical meanings.Therefore,to fit our rhBMP-2 quantification data,we applied two logistic regression models,three-parameter log-logistic model and four-parameter log-logistic model.The four-parameter log-logistic model(adj-R2>0.98)fits better than three-parameter log-logistic model(adj-R2>0.75)for the sigmoid curves.Overall,our results indicate rhBMP-2 quantification in vitro can be accomplished by detecting ALP activity and fitting four-parameter log-logistic model.Furthermore,we also provide a highly adaptable R script for any additional logistic models.

关 键 词：rhBMP-2 bioactivity quantification statistical model fitting R programming 

分 类 号：R318[医药卫生—生物医学工程]